This is a renewal application for support of the Yale University Digestive Disease Research Core Center, a multidisciplinary Center whose research focus is Liver Structure, Function and Disease. Fifty independently funded investigators comprise a current digestive disease related research base of ~ $27 million. Research programs in the Center are distributed in 15 departments of the University including Biomedical and Chemical Engineering and Physiology;Cell Biology;Cellular and Molecular Physiology;Comparative Medicine;Epidemiology and Public Health;Human Genetics;Immunobiology;Laboratory Medicine;Internal Medicine;Microbial Pathogenesis;Molecular, Cellular and Developmental Biology;Pathology;Pediatrics;Pharmacology;Radiology and Surgery. The research base continues to focus on six major areas: 1) Cellular and Molecular Biology of the Liver. 2) Hepatic Transport Mechanisms. 3) Basic Biology of Disease Processes. 4) Studies of the Splanchnic Circulation 5) Liver Immunology and 6) Clinical Hepatology. The research programs are broad and range from fundamental studies of the biology of liver and other cells to translational studies of immediate clinical relevance. The major goals of the Center continue to be: 1) to stimulate multidisciplinary interactions between basic and clinical faculty and departments 2) to provide and in-depth training environment 3) to efficiently organize time consuming, often costly techniques and procedures in Core Facilities for use by multiple investigators 4) to stimulate basic scientists to direct their focus to areas of interest to the Center 5) to stimulate translational research from bench to bedside 6) to promote new research and training opportunities with a pilot feasibility program, and 7) to create an intellectual environment within the field by fostering collaborations both within and outside the institution and through its enrichment program. To achieve these goals the Center is organized into 4 Core Facilities including: 1) Administrative Core 2) Cellular and Molecular Physiology Core 3) Morphology Core and 4) A Clinical Translational Core. A Pilot Feasibility Program supports 1-2 year small grants for new scientific initiatives. The Enrichment Program consists of research seminars, symposia, and retreats.